Can Ivabradine be recommended in the management of acute heart failure complicating myocardial infarction?

Transcription

1 Can Ivabradine be recommended in the management of acute heart failure complicating myocardial infarction? Rajagopal Jambunathan MD, DM Vikram Hospital and Heart Care Mysore, India

2 Conflicts of Interest NONE TO DECLARE NOT RECEIVED ANY GRANTS

3 Background: Sinus Tachycardia is an independent predictor of mortality following acute myocardial infarction (MI) Many situations, like acute heart failure complicating myocardial infarction demand rate control but beta blockers cannot be used, often due to low or borderline blood pressures This problem is further compounded by the use of ionotropes

4 Ivabradine Selective I(f) antagonist Pure Sinus rate reduction Ivabradine has the potential advantage of reducing heart rate without lowering blood pressures in these acute situations Presently it is contraindicated in Acute MI and shock due to lack of data Contraindicated in Inferior wall MI

5 In our initial observational study, we had found that Ivabradine may have role in acute heart failure (Presented at ACC 2010) Reduced duration of ionotropic support Reduced recurrent symptoms of heart failure In acute anterior wall MI also, it brought down the heart rate, without any appreciable side effects

6 Concept we proposed to Verify: Ivabradine is safe and beneficial in the management of Acute heart failure with Acute Anterior wall MI

7 Materials and Methods: Inclusion Criteria: Patients with an acute anterior wall MI with: a heart rate of more than 100/min Systolic blood pressure < 100mmHg including cardiogenic shock one or more signs of Left ventricular failure requiring ionotropic support or having any other contraindications to beta-blockers were given Ivabradine (5 to 7.5mg twice daily P.O.) Similar patients who did not receive Ivabradine formed the control group

8 The rest of the treatment was as per standard protocol in our intensive care unit for both groups We studied the hemodynamics in both groups and follow up was limited to index hospitalisation

9 Exclusion Criteria: Mortality within 24 hours of admission Sustained ventricular or atrial arrhythmia AV blocks or sinus bradycardia at any time before randomization NSTEMI or NQMI ( except LBBB)

10 Statistical analyses Data was entered onto MS Excel worksheet Analyzed using SPSS 12.0 software Statistical tests of significance was done using Chi Square test for qualitative variables Test of normality was done using Shapiro-Wilk test Independent samples t Test for normally distributed quantitative variables Mann-Whitney U test (non-parametric) for quantitative variables not normally distributed.

11 Results: Primary Efficacy End points: Mean Heart rate reduction Duration of Ionotropic support required Mean Troponin rise over first 24 hours Secondary end points: (Safety) Recurrent angina and Re-infarction Recurrent symptoms and signs of heart failure All cause mortality

12 Results: (n =390) Ivabradine (n=187) Control (n=203) Age (mean) years 56.6 years NS Symptoms to admission duration hours hours NS Thrombolysis NS PCI NS P

13 Mean Age in years among the study groups Group Mean Age in years S.D 95% C.I Control Ivabradine p=0.975

14 Distribution of the study group based on sex Control Ivabradine 10 0 Male Female Total p=0.292]

15 Mean Time in hours from symptom onset to admission p=0.83

16 Thrombolysis p=0.413

17 PCI (Both primary and rescue) p=0.804 NS

18 Ventilator Requirement n=54 n=49 p=0.929 NS

19 Requirement of Ionotrope support n=172 n=155 p=0.622, NS

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21 Our Findings: Mean heart rate reduction in beats per minute among study groups Group Mean HR reduction in bpm S.D 95% C.I Control Ivabradine p=0.000, significant.

22 Mean heart rate reduction in beats per minute among study groups

23 Mean duration of Ionotrope support in hours among study groups Group Mean duration S.D 95% C.I Control Ivabradine p=0.000, significant

24 Mean Troponin I (ng/ml) rise in 24 hours among study groups P <0.0001

25 Secondary End Points: Recurrent Angina and Reinfarction n=55 n=26 p=0.001, significant

26 Secondary End Points: Recurrence of Heart Failure within index hospitalization n=39 n=14 p=0.001, significant

27 Secondary End point: Mortality n=34 n=19 p=0.058 not significant

28 Mortality Analysis: Recurrent Heart failure Deaths in Control (n=34) 1 (2.9%) 0 Deaths in Ivabradine (n=19) Recurrent Angina/Re-MI Recurrent HF + Re- MI 18 (52.9%) 13 (68.4 %) 13 (37.9%) 04 (21.1%) Sudden Cardiac death 2 (5.8%) 2 ( 10.5%)

29 Combined end points: Control Ivabradine Total No death/rec HF/Rec angina/mi Rec HF only Rec angina/reinfarction only Death only Rec HF and Rec angina/reinfarction only Rec HF and Death only Rec angina/reinfarction and Death only Rec HF + Rec angina/reinfarction Death Total

30 Occurrence of Recurrent angina/mi, recurrent heart failure and death together n=13 n=4 p=0.039 significant

31 Conclusions: In patients with Heart failure accompanying acute anterior wall MI, ivabradine : Effectively controls the heart rate preventing excessive sinus tachycardia even with ionotropes Reduces the infarct size probably secondary to control of heart rate Reduces the duration of Ionotrope use

32 Reduces recurrent heart failure symptoms Reduces a combined end point of death, recurrent angina/re-infarction, recurrent heart failure No significant reduction in mortality

33 CONCLUSION: In this interventional study, Ivabradine, by selectively controlling heart rate, seems to be a valuable addition in management of heart failure complicating Acute Myocardial infarction in reducing infarct size and in-hospital events in patients ineligible for beta-blocker therapy It needs to be validated in further randomized studies

34 Special Thanks: Co Authors Arun Srinivas, Keshavamurthy CB, Guruprasad HP, Naveen K H, Arjun Adnaik R Statistician: Murali Dhar, M.Sc, M.Phil, Ph.D, PG(Epidemiology, Finland)

35 VIKRAM HOSPITAL AND HEART CARE, MYSORE, INDIA